Document Detail

Helicobacter pylori VacA Reduces the Cellular Expression of STAT3 and Pro-survival Bcl-2 Family Proteins, Bcl-2 and Bcl-X(L), Leading to Apoptosis in Gastric Epithelial Cells.
MedLine Citation:
PMID:  20927590     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Helicobacter pylori vacuolating cytotoxin, VacA, stimulates apoptosis via a mitochondria-dependent pathway. VacA induces apoptosis via activation of the pro-apoptotic B-cell lymphoma (Bcl)-2 family proteins, Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), while the implication of such pro-survival Bcl-2 family members as Bcl-2 and Bcl-X(L) in the VacA-induced apoptosis remains unknown. Signal transduction and activator of transcription 3 (STAT3) is a pivotal transcription factor that upregulates Bcl-2 and Bcl-X(L).
AIMS: This study was conducted to elicit the implication of STAT3 and pro-survival Bcl-2 and Bcl-X(L) in the intrinsic apoptosis.
METHODS: Immunoblot and reverse transcriptase real-time polymerase chain reaction (RT-PCR) were employed to assess the cellular expression of STAT3, Bcl-2, and Bcl-X(L) in response to purified VacA in gastric adenocarcinoma cell lines. VacA-induced apoptosis was quantitated morphologically following knockdown by each specific small interfering RNA (siRNA) or in the presence of pharmacological inhibitors.
RESULTS: VacA reduced STAT3, Bcl-2, and Bcl-X(L) expression in a dose-dependent manner. Knockdown of STAT3, Bcl-2, and Bcl-X(L) by siRNA induced apoptosis to a similar extent in the case of sufficient VacA inoculation. The VacA-mediated reduction of STAT3 expression was independent of cellular vacuolization, since a vacuolar-type ATPase inhibitor, bafilomycin A1, did not inhibit VacA-induced reduction of STAT3, Bcl-2, and Bcl-X(L) expression. Instead, a c-JUN NH(2)-terminal kinase (JNK) inhibitor, SP600125, restored the VacA-induced reduction of STAT3 expression to the basal level.
CONCLUSIONS: VacA-induced apoptosis may be, in part, implicated in the reduction of STAT3 linking to the downregulation of Bcl-2 and Bcl-X(L), in association with JNK activity.
Ayako Matsumoto; Hajime Isomoto; Masaaki Nakayama; Junzo Hisatsune; Yoshito Nishi; Yujiro Nakashima; Kayoko Matsushima; Hisao Kurazono; Kazuhiko Nakao; Toshiya Hirayama; Shigeru Kohno
Publication Detail:
Type:  Journal Article     Date:  2010-10-07
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  56     ISSN:  1573-2568     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  999-1006     Citation Subset:  AIM; IM    
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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